Expression of transcription factors CREB and c-Fos in the brains of terminal Creutzfeldt-Jakob disease cases

Expression levels and localization of transcription factors cAMP response element binding protein (CREB1 and CREB2) and c-Fos, as well as levels of up-stream mitogen-activated protein kinases/extracellular signal-regulated kinases (ERK-1 and ERK-2) and p38 kinase, were examined in the brains (frontal cortex) of eleven cases with Creutzfeldt-Jakob disease (CJD) and five age-matched controls. Preserved expression levels of ERK-1-P, ERK-2-P and p38-P were observed in CJD. However, significantly reduced levels, as revealed by gel electrophoresis and Western blotting, and reduced numbers of immunoreactive nuclei, as seen by immunohistochemistry, to CREB, CREB-P, c-Fos and c-Fos-P were found in CJD when compared with controls. These observations point to exhausted CREB and c-Fos brain responses, in spite of preserved up-stream signaling kinases, thus favoring cell death in terminal stages of CJD.